The objectives of the proposed research are to elucidate the functional roles of cyclic GMP-dependent protein kinase (G-PK) and its stimulatory modulator in normal and malignant cell proliferation. The experimental models to be employed are: the Morris hepatoma 3924A (vs. normal liver), and the Morris hepatoma 9618A (vs. normal liver), the fast- and slow-growing hepatomas, respectively, and regenerating liver (vs. sham-operated liver) in rats. Attempts will be made to seek, characterize or identify possible changes in patterns, localizations and properties or species of G-PK and its stimulatory modulator, as well as those of endogenous substrate protein of G-PK, in cells undergoing proliferation. The above parameters will be compared to those obtained for cyclic AMP-dependent protein kinase (A-PK) and its inhibitory modulator (protein inhibitor). It is hoped that the proposed studies would shed light on roles of G-PK and A-PK, presumably the physiologic target enzymes for cyclic GMP and cyclic AMP, in the process or regulation of cell proliferation.